Abstract
PURPOSE: To investigate the effect of a monoclonal antibody (CH12), targeted against epidermal growth factor receptor type III variant (EGFRvIII), on human ovarian cancer cells when administered in combination with cisplatin chemotherapy. METHODS: Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to determine the expression levels of EGFRvIII protein and mRNA, respectively, in the ovarian cancer cell lines SK-OV-3 and CAOV-3. Cells were left untreated or treated with either cisplatin or CH12 alone or both agents in combination (2 μg/ml cisplatin plus CH12). Cell proliferation was detected in a CCK-8 assay. The binding affinities of the CH12 mAb to the 2 cell lines were analyzed; after treatment with cisplatin and different concentrations of CH12, the apoptotic ratios and cell cycle stages of SK-OV-3 cells were determined by flow cytometry (FCM). RESULTS: The express of EGFRvIII mRNA and protein in the two ovarian cancer cell lines were both detected. Analysis of the combination index yielded a value of 0.915, indicating that 2 drugs have a synergistic therapeutic effect. SK-OV-3 cells were observed to be much more resistant to cisplatin than CAOV-3 cells. The primary combinatorial effect of the 2 drugs was the induction of apoptosis, but we also observed synergic co-inhibition of the cell cycle of SK-OV-3 in the S phase. CONCLUSIONS: We conclude that CH12 antibody is a promising candidate for clinical therapy for ovarian cancer cells, which has lower sensitivity to cisplatin treatment; however, the underlying mechanism needs further study.